Efficacy and Safety Study of SyB L-0501 for Patients With Chronic Lymphocytic Leukemia

Inclusion Criteria

Patients meeting all of the following criteria are to be included in the study:

1. Patients aged between 20 and 80 years (at the time of registration)
2. Patients who have provided written consent in person for participation in this study
3. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
4. Patients who are expected to survive for at least 3 months
5. Patients who are naive to or not suitable for fludarabine therapy
6. Patients who are documented with chronic lymphocytic leukemia on the basis of International Workshop on Chronic Lymphocytic Leukaemia guideline (IWCLL) guideline:

   * The presence of ≥ 5000/mm3 monoclonal mature B-lymphocytes in the peripheral blood
   * ≤ 55 % atypical lymphocytes, prolymphocyte-like cells, and lymphoblasts with prominent nucleoli
   * For monoclonal mature B-lymphocytes, at least one of the B-cell specific differentiation antigens (Cluster of differentiation (CD) 19, CD 20, and CD 23) and CD 5 is positive by flow cytometry
7. Patients in Stage C or stage B with active disease based on Binet staging system (at the time of registration)

   * Decision to start treatment should be made upon IWCLL guideline criteria.
   * Active disease is defined to meet at least one of the following criteria.

     1. Progression and/or worsening of anemia and/or thrombocytopenia caused by decreased bone marrow function.
     2. Massive (6 cm below the left costal margin) or progressive or symptomatic splenomegaly
     3. Massive nodes (≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy
     4. Progressive lymphocytosis with an increase of \> 50% over a 2-month period, or lymphocyte doubling time of less than 6 months
     5. Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids or other standard therapy
     6. B symptoms Weight loss \> 10% within the previous 6 months Fevers of greater than 38.0° C for 2 or more weeks without other evidence of infection Night sweats
8. Patients with 2 or less regimens of previous chemotherapy including antibody therapy. Corticosteroid monotherapy is not counted.
9. Patients with adequately maintained organ functions (e.g., bone marrow, heart, lung, liver, and kidney functions)

   * Neutrophil count: ≥ 1,000 /mm3
   * Aspartate aminotransferase(AST) Glutamic oxaloacetic transaminase(GOT): ≤ 3.0 times the upper limit of normal range at each site
   * Alanine aminotransferase (ALT) Glutamic pyruvic transaminase(GPT): ≤ 3.0 times the upper limit of normal range at each site
   * Total bilirubin: ≤ 1.5 times the upper limit of normal range at each site
   * Serum creatinine: ≤ 1.5 times the upper limit of normal range at each site
   * Partial pressure of O2 (PaO2): ≥ 65 mmHg
   * No abnormalities which require treatment are detected on ECG
   * Left ventricular ejection fraction (LVEF) (echocardiography): ≥ 55%

Exclusion Criteria:

Patients who fall under any one of the following criteria are to be excluded

1. Patients who have been without treatment for less than 4 weeks after prior treatment. For patients treated with antibody therapy or underwent hematopoietic stem cell transplantation, for 3 months after prior treatment
2. Patients who enrolled other clinical studies within 4 weeks before registration for this study
3. Patients who received allogeneic stem cell transplantation in the past
4. Patients with defective p53 (17p-) confirmed by chromosome analysis (Fluorescence in situ hybridization (Fish) method)
5. Patients who are clinically diagnosed with Richter's syndrome
6. Patients with infiltration to the central nervous system (CNS) or patients with clinical symptoms of suspected infiltration to the CNS
7. Patients with multiple primary cancers or patients with a history of other malignant tumors within past 5 years, except for basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix or gastrointestinal tract
8. Patients with serious bleeding tendencies (e.g., disseminated intravascular coagulation (DIC))
9. Patients with, or confirmed in the past to have had, interstitial lung disease or pulmonary fibrosis
10. Patients with, or confirmed in the past to have had, autoimmune hemolytic anemia responds to corticosteroid therapy
11. Patients with any of the following complications

    * serious cardiac disease (e.g., myocardial infarction, ischemic heart disease, or arrhythmia requiring treatment)
    * serious, active infections (requiring intravenous administration of antibiotics, antifungal drugs, or antiviral drugs)
    * hepatic or renal dysfunction
    * accumulation of pleural effusion, pericardial effusion, or peritoneal effusion
    * uncontrollable serious gastrointestinal disease, endocrine disorder, or mental illness
12. Patients who received SyB L-0501 in the past
13. Patients with allergies to mannitol
14. Patients who need cytokine preparations such as erythropoietin or granulocyte colony stimulating factor (G-CSF) or blood transfusions at registration for this study
15. Patients positive for HIV antibody or Hepatitis C virus (HCV) antibody
16. Patients positive for Hepatitis B surface (HBs) antigen. Patients with negative results will also be checked for Hepatitis B core (HBc) antibody and HBs antibody. If either of the test results is positive, measure Hepatitis B virus (HBV)-DNA and exclude the patients with results above sensitivity
17. Patients with clinical symptom of cytomegalovirus (CMV) infection, except asymptomatic patients with CMV positive
18. Patients who are pregnant, who may possibly be pregnant, or lactating
19. Patients who do not agree to practice contraception. Male: During investigational product administration and until 6 months after final administration Female: During investigational product administration and until 4 months after final administration
20. Patients with drug addiction, narcotics addiction, and/or alcohol dependency
21. Patients otherwise judged by the investigator or sub-investigator to be unsuitable for inclusion in this study